“Neonatal seizure: how reliable is its diagnosis and treatment? A mini review of previous knowledge”

Seizure is the most common neurologic event in the neonatal period when the immature, growing brain is vulnerable to various injuries. Seizure might be present as an atypical feature in neonates, which makes diagnosis a challenge. A vast majority of seizures are symptomatic due to an underlying cause, searching for etiology to remove them leads to more effective therapy. However, there is doubt about the diagnosis of seizures and the best treatment for them. Here, we reviewed articles related to diagnosis and treatment of neonatal seizures to evaluate the available evidence. The results showed that despite numerous studies on the topic, neither an implicit diagnosing method nor a therapeutic regime was proposed. It was also observed that phenobarbital prescription was reduced while newer anti-seizure medication such as levetiracetam was further prescribed. Seizure, the most common neurologic disorder in neonates, is a challenging topic for both neonatologists and neurologists. Since patients are critically ill, designing a randomized clinical trial appears not to be easy for neonates admitted to a neonatal intensive care unit. Moreover, both the diagnosis and treatment of seizures should be re-evaluated based on neonatal characteristics. In the recent decade, new less harmful anti-seizure medications are being replaced with old ones.

Iran J Child Neurol. Autumn 2020 Vol. 14 No. 4 in neonatal seizures is obligatory for both diagnosis and treatment monitoring is obligatory not optional.
Several studies suggest that neonatal seizures could be considered as a biomarker for brain function and not only as a disease. This is another major feature of neonatal electrographic seizure evolution that could be observed in frequency, morphology, and voltage (9). EEG video monitoring is gold standard for detection of neonatal seizures. However, it is not easily available commercially and there is a limited number of trained operators and interpreters to implement it (9). Amplitude integrated EEG (aEEG) is another technique which has been used since 1990 in the neonatal intensive care unit (NICU) (10) as a useful screening method for brain function monitoring (11). Brain signals are amplified and pass through a band pass filter, which make a semi-logarithmic scale that is easier to interpret for untrained caregivers because pattern recognition could be performed more easily compared with conventional EEG. In contrast, the accuracy and sensitivity of aEEG are a challenging topic (6). Many infrequent, low amplitude brief seizures might be missed by using EEG (12). On the other hand, focal seizures that are beyond the surface and are covered by an EEG with electrode are not detected (2).
There is no consensus among neonatologists and neurologists regarding the treatment for clinical/ electrographic seizures, the first drug of choice, and the use of EEG to diagnose and determine the treatment duration after cessation of seizures. It is controversial whether neonatal seizures, without considering underlying injury, lead to brain damage (5). It is not widely accepted that treatment of electrographic seizures per se is followed by better prognosis (13-16). Furthermore, results of data was concerning neonatal seizure.
The immature brain is more vulnerable to seizure due to several factors such as primary development of excitatory neurotransmitters, delayed inhibition of GABA neurotransmitters, and increase of excitatory glutaminergic neurons (2). The developing brain is considered as a great topic for debate: "how vulnerable or resistant is it to injuries such as seizures". In most cases, an acute event leads to neonatal seizure, including Hypoxic Ischemic Encephalopathy (HIE), the  Several surveys declare that levetiracetam not only is effective in the control of neonatal seizures (38,39), but also has fewer side effects compared to phenobarbital (40)(41)(42)34 or organ failure (43). Some of its side effects such as mild sedation, nutritional disturbances, mild apnea/bradycardia, and diminishment of urine output are considered theoretically, but are not reported in clinical cases (43,44). Levetiracetam could be effective in neonatal seizure control up to 63%, while it is reported to have minor adverse effects (e.g., drowsiness, irritability, and transient conjugate hyperbilirubinemia) (45,9). been established yet (46). Some experts believe that medications should be simplified as a sole drug before hospital discharges, or even, should be discontinued in acute seizures (47). However, others continue medications for several months despite their adverse effects (48).
Neonatal seizures are the most common neurologic manifestations in the neonatal period. In the majority of cases, there is an acute brain insult, leading to seizures such as HIE that is by far the most common etiology. It is a common issue to encourage further collaboration of neonatologists and neurologists. Since no precise definition is available for seizure diagnosis and treatment, there are much of aspects in debates. In recent years, there has been a shift from mortality to morbidity.